Valproic Acid For Refractory Post-Traumatic Dizziness and Photopsia
DOI:
https://doi.org/10.19166/lijn.v1i3.10388Keywords:
Post-Concussion Syndrome, Valproic Acid, Mild Traumatic Brain Injury, Vestibular Symptoms, Visual DysfunctionAbstract
Introduction: Post-concussion syndrome (PCS) is a collection of cognitive, vestibular, and visual symptoms that may persist after mild traumatic brain injury (mTBI). Current management is largely supportive, highlighting the need for alternative pharmacologic approaches. This case report explores the therapeutic potential of valproic acid (VPA), a compound with neuroprotective and anti-inflammatory effects.
Case Presentation: A 28-year-old woman presented with persistent vertigo and visual disturbances, including photopsia, following a mild head injury sustained in a motor vehicle accident. Neurological examination and imaging were unremarkable. Symptomatic therapies provided only partial and temporary relief, prompting the trial of VPA. The patient subsequently experienced gradual clinical improvement, achieving complete symptom resolution within six months and maintaining remission after discontinuation of treatment.
Discussion: The patient’s symptoms were attributed to functional disturbances involving the occipital cortex and vestibular pathways, commonly implicated in PCS. Hypothesized contributors included ionic disequilibrium, cortical hyperexcitability, and neuroinflammatory processes. Beyond its traditional use as an antiepileptic, VPA may offer therapeutic advantages in PCS through GABAergic modulation, Histone Deacetylase (HDAC) inhibition, and anti-inflammatory actions.
Conclusions: This case highlights VPA as a promising pharmacologic option for refractory PCS. However, further studies are required to determine its efficacy, optimal dosage, and safety profile in this setting.
Keywords: Post-Concussion Syndrome; Valproic Acid; Mild Traumatic Brain Injury; Vestibular Symptoms; Visual Dysfunction
References
1. Permenter CM, Thomas RJF, Sherman AL. Postconcussive Syndrome. Sport Concussion Diagnosis Manag Second Ed [Internet]. 2023 Aug 28 [cited 2025 Aug 6];99–130. Avalaible from: https://doi.org/10.1212/01.CON.0000458974.78766.58
2. Renga V. Clinical Evaluation and Treatment of Patients with Postconcussion Syndrome. Neurol Res Int. 2021;2021. Available from: https://doi.org/10.1155/2021/5567695
3. van der Vlegel M, Polinder S, Toet H, Panneman MJM, Haagsma JA. Prevalence of post-concussion-like symptoms in the general injury population and the association with health-related quality of life, health care use, and return to work. J Clin Med [Internet]. 2021 Feb 2 [cited 2025 Aug 6];10(4):1–18. Available from: https://doi.org/10.3390/jcm10040806
4. Suwaryo PAW, Kadir F, Omar A, Singh SKD. Prevalence of Persistent Post-Concussion Syndrome in Adults After Mild Traumatic Brain Injury. Nurse Media J Nurs [Internet]. 2024 Aug 31 [cited 2025 Aug 6];14(2):199209. Available from: https://doi.org/10.14710/nmjn.v14i2.56529
5. Balakrishnan B, Rus R, Chan K, Martin A, Awang M. Prevalence of Postconcussion Syndrome after Mild Traumatic Brain Injury in Young Adults from a Single Neurosurgical Center in East Coast of Malaysia. Asian J Neurosurg [Internet]. 2019 Mar [cited 2025 Aug 6];14(1):201–5. Available from: https://doi.org/10.4103/ajns.AJNS_49_18
6. Vibol Bo, Pearkao C. Post-Concussion Syndrome and Factors Associated With Post- Concussion Syndrome Following Mild Traumatic Brain Injury. Med Leg Updat. 2021 Jun 3;21(3):99–108. Available from: https://doi.org/10.37506/mlu.v21i3.2970
7. Harrell RG, Manetta CJ, Gorgacz MP. Dizziness and Balance Disorders in a Traumatic Brain Injury Population: Current Clinical Approaches. Curr Phys Med Rehabil Reports [Internet]. 2021 Jun 1 [cited 2025 Aug 6];9(2):41–6. Available from: https://doi.org/10.1007/s40141021-00308-5
8. Andersson H, Jablonski GE, Nordahl SHG, Nordfalk K, Helseth E, Martens C, et al. The Risk of Benign Paroxysmal Positional Vertigo After Head Trauma. Laryngoscope [Internet]. 2022 Feb 1 [cited 2025 Aug 6];132(2):443–8. Available from: https://doi/pdf/10.1002/lary.29851
9. Gianoli GJ. Post-concussive Dizziness: A Review and Clinical Approach to the Patient. Front Neurol [Internet]. 2022 Jan 4 [cited 2025 Aug 6];12. Available from: https://doi.org/10.3389/fneur.2021.718318
10. Debacker J, Ventura R, Galetta SL, Balcer LJ, Rucker JC. Neuro-ophthalmologic disorders following concussion. Handb ClinNeurol [Internet]. 2018 Jan 1 [cited 2025 Aug 6];158:145–52. Available from: https://doi.org/10.1016/B978-0-44463954-7.00015-X
11. Gunasekaran P, Hodge C, Rose K, Fraser CL. Persistent visual disturbances after concussion. AustGenPract [Internet]. 2019 Aug 1 [cited 2025 Aug 6];48(8):5316. Available from: https://doi.org/10.31128/AJGP-03-194876
12. Master CL, Scheiman M, Gallaway M, Goodman A, Robinson RL, Master SR, et al. Vision Diagnoses Are Common after Concussion in Adolescents. Clin Pediatr(Phila) [Internet]. 2016 Mar 1 [cited 2025 Aug 6];55(3):260–7. Available from: https://doi.org/10.1177/0009922815594367
13. Farah A. Pharmacology and natural therapies for postconcussion syndrome. Psychiatr Ann [Internet]. 2017 Feb 1 [cited 2025 Aug 6];47(2):83–7. Available from: https://doi.org/10.3928/0048571320170103-02
14. Kim K, Priefer R. Evaluation of current post concussion protocols. Biomed Pharmacother [Internet].2020 Sep 1 [cited 2025 Aug 6];129. Available from: https://doi.org/10.1016/j.biopha.2020.11 0406
15. Hummel R, Dorochow E, Zander S, Ritter K, Hahnefeld L, Gurke R, et al. Valproic Acid Treatment after Traumatic Brain Injury in Mice Alleviates Neuronal Death and Inflammation in Association with Increased Plasma Lysophosphatidylcholines. Cells [Internet]. 2024 May 1 [cited 2025 Aug 5];13(9):734. Available from: https://doi.org/10.3390/cells13090734
16. Bedaso A, Geja E, Ayalew M, Oltaye Z, Duko B. Post-concussion syndrome among patients experiencing head injury attending emergency department of Hawassa University Comprehensive specialized hospital, Hawassa, southern Ethiopia. J Headache Pain [Internet]. 2018 Nov 21 [cited 2025 Aug 6];19(1):112. Available from: https://doi.org/10.1186/s10194-0180945-0
17. Hadanny A, Efrati S. Persistent postconcussion syndrome: pathophysiology, diagnosis, current and evolving treatment strategies. Expert Rev Neurother [Internet]. 2025 Aug 3 [cited 2025 Aug 6]; Available from: https://doi.org/10.1080/14737175.2025.2515061
18. Polinder S, Cnossen MC, Real RGL, Covic A, Gorbunova A, Voormolen DC, et al. A Multidimensional Approach to Post concussion Symptoms in Mild Traumatic Brain Injury. Front Neurol [Internet]. 2018
[cited 2025 Aug 6];9. Available from: https://doi.org/10.3389/fneur.2018.01113
19. Harmon KG, Drezner J, Gammons M, Guskiewicz K, Halstead M, Herring S, et al. American medical society for sports medicine position statement: Concussion in sport. Clin J Sport Med [Internet]. 2013
Jan [cited 2025 Aug 6];23(1):1–18. Available from: https://doi.org/10.1136/bjsports-2012091941
20. Danielli E, Simard N, DeMatteo CA, Kumbhare D, Ulmer S, Noseworthy MD. A review of brain regions and associated post-concussion symptoms. Front Neurol [Internet]. 2023 [cited 2025 Aug 6];14. Available from: https://doi.org/10.3389/fneur.2023.1136367
21. Grabowski P, Wilson J, Walker A, Enz D, Wang S. Multimodal impairment-based physical therapy for the treatment of patients with post-concussion syndrome: A retrospective analysis on safety and feasibility. Phys Ther Sport [Internet]. 2017 Jan 1[cited 2025 Aug 6];23:22–30. Available from: https://doi.org/10.1016/j.ptsp.2016.06.001
22. Tal S, Hadanny A, Sasson E, Suzin G, Efrati S. Hyperbaric oxygen therapy can induce angiogenesis and regeneration of nerve fibers in traumatic brain injury patients. Front Hum Neurosci [Internet]. 2017 Oct 19 [cited 2025 Aug 6];11:270271. Available from: https://doi.org/10.3389/fnhum.2017.00508
23. Kozlov A V., Javadov S, Sommer N. Cellular ROS and Antioxidants: Physiological and Pathological Role. Antioxidants [Internet]. 2024 May 1 [cited 2025 Aug 6];13(5). Available from: https://doi.org/10.3390/antiox13050602
24. Jelinek M, Jurajda M, Duris K. Oxidative stress in the brain: Basic concepts and treatment strategies in stroke. Antioxidants [Internet]. 2021 Dec 1 [cited 2025 Aug 6];10(12). Available from: https://doi.org/10.3390/antiox10121886
25. Borich MR, Brodie SM, Gray WA, Ionta S, Boyd LA. Understanding the role of the primary somatosensory Opportunities for cortex: rehabilitation. Neuropsychologia [Internet]. 2015 Dec 1 [cited 2025 Aug 6];79(Pt B):246–55. Available from: https://doi.org/10.1016/j.neuropsychologia.2015.07.007
26. Trofimova A, Smith JL, Ahluwalia V, Hurtado J, Gore RK, Allen JW. Alterations in Resting-State Functional Brain Connectivity and Correlations with Vestibular/Ocular Motor Screening Measures in Postconcussion Vestibular Dysfunction. J Neuroimaging [Internet]. 2021 Mar 1 [cited 2025 Aug 6];31(2):277–86. Available from: https://doi.org/10.1111/jon.12834
27. Johnson B, Hallett M, Slobounov S. Follow up evaluation of oculomotor performance
with fMRI in the subacute phase of concussion. Neurology [Internet]. 2015 Sep 29 [cited 2025 Aug 6];85(13):1163–6. Available from: https://doi.org/10.1212/WNL.0000000000001968.
28. Virdee J, Mollan SP. Photopsia. Pract Neurol [Internet]. 2020 Oct 1 [cited 2025 Aug 6];20(5):415–9. Available from: https://doi.org/10.1136/practneurol 2019-002460
29. Ciuffreda KJ, Han MHE, Tannen B, Rutner D. Visual snow syndrome: Evolving neuro optometric
considerations in concussion/mild traumatic brain injury. Concussion [Internet]. 2021 Jun 1 [cited 2025 Aug 6];6(2). Available from: https://doi.org/10.2217/cnc-2021-0003
30. Chen BS, Lance S, Lallu B, Anderson NE. Visual snow: Not so benign. J Clin Neurosci [Internet]. 2019 Jun 1 [cited 2025 Aug 6];64:37–9. Available from: https://doi.org/10.1016/j.jocn.2019.03.023
31. Rauchman SH, Zubair A, Jacob B, Rauchman D, Pinkhasov A, Placantonakis DG, et al. Traumatic brain injury: Mechanisms, manifestations, and visual sequelae. Front Neurosci [Internet]. 2023 [cited 2025 Aug 6];17. Available from: https://doi.org/10.3389/fnins.2023.1090672
32. Verhoekx JSN, van Overdam KA, Gishti O, van Leeuwen R, & Crama, N. Plotsetoename van mouches volantes is een alarmsymptoom, ook zónder lichtflitsen [Acute onset of floaters, even without flashes, is an urgent ophthalmic warning sign]. Nederlands tijdschrift voor geneeskunde [Internet]. 2021 [cited 2025 Aug 6];165. Available from: https://pubmed.ncbi.nlm.nih.gov/34854588/.
33. Wallace B, Lifshitz J. Traumatic brain injury and vestibulo-ocular function: Current challenges and future prospects. Eye Brain [Internet]. 2016 [cited 2025 Aug 6];8:15364. Available from: https://doi.org/10.2147/EB.S82670
34. Renga V. Clinical Evaluation of Patients with Vestibular Dysfunction. Neurol Res Int [Internet]. 2019 [cited 2025 Aug 6];2019. Available from: https://doi.org/10.1155/2019/3931548
35. Akin FW, Murnane OD, Hall CD, Riska KM. Vestibular consequences of mild traumatic brain injury and blast exposure: a review. Brain Inj [Internet]. 2017 Jul 29 [cited 2025Aug 6];31(9):1188–94. Available from: https://doi.org/10.1080/02699052.2017.1288928
36. Taylor RL, Wise KJ, Taylor D, Chaudhary S, Thorne PR. Patterns of vestibular dysfunction in chronic traumatic brain injury. Front Neurol [Internet]. 2022 Dec 1 [cited 2025 Aug 6];13. Available from: https://doi.org/10.3389/fneur.2022.942349
37. Gard A, Al-Husseini A, Kornaropoulos EN, De Maio A, Tegner Y, Björkman-Burtscher I, et al. Post-Concussive Vestibular Dysfunction Is Related to Injury to the Inferior Vestibular Nerve. J Neurotrauma [Internet]. 2022 Jun 1 [cited 2025 Aug 6];39(11–12):829–40. Available from: https://doi.org/10.1089/neu.2021.0447
38. Campbell KR, Parrington L, Peterka RJ, Martini DN, Hullar TE, Horak FB, et al. Exploring persistent imbalance complaints of after mTBI: Oculomotor, peripheral vestibular and central sensory integration function. J Vestib Res Equilib Orientat [Internet]. 2021 [cited 2025 Aug 6];31(6):519–30. Available from:
https://doi.org/10.3233/VES-201590
39. Von Brevern M, Bertholon P, Brandt T, Fife T, Imai T, Nuti D, et al. Benign paroxysmal
positional vertigo: Diagnostic criteria. J Vestib Res Equilib Orientat [Internet]. 2015 Oct 15 [cited 2025 Aug 6];25(3–4):105–17. Available from: https://doi.org/10.3233/VES-150553
40. Józefowicz-Korczynska M, Pajor A, Skóra W. Benign paroxysmal positional vertigo in patients after
mild traumatic brain injury. Adv Clin Exp Med [Internet]. 2018 Oct 1 [cited 2025 Aug 6];27(10):1355–9. Available from: https://doi.org/10.17219/acem/69708
41. Sivakumar J. Approach to imaging in mild traumatic brain injury. J Case Reports Images Surg J Case
Rep Images Surg [Internet]. 2017;33(2):61–3. Available from: https://doi.org/10.5348/Z12-201751-RA-16
42. Alouani AT, Elfouly T. Traumatic Brain Injury (TBI) Detection: Past, Present, and Future. Biomedicines [Internet]. 2022 Oct 1 [cited 2025 Aug 6];10(10). Available from: https://doi.org/10.3390/biomedicines10102472
43. Haneef Z, Levin HS, Frost JD, Mizrahi EM. Electroencephalography and quantitative electroencephalography in mild traumatic brain injury. J Neurotrauma [Internet]. 2013 Apr 15 [cited 2025 Aug 6];30(8):6536. Available from: https://doi.org/10.1089/neu.2012.2585
44. Ianof, J. N., & Anghinah, R. (2017). Traumatic brain injury: An EEG point of view. Dementia & neuropsychologia, 11(1), 3–5. Available from: https://doi.org/10.1590/198057642016dn11-010002
45. Perhimpunan Dokter Spesialis Saraf Indonesia. Pedoman Praktik Klinis Neurologi 2023. 1st ed. Kurniawan M, Ganiem AR, Wiratman W, editors. Jakarta; 2023. 1–626 p. Available from: https://perdosni.org/unduhan/kategori_download/p2kb/
46. Ontario Neurotrauma Foundation. Guidleines for mild traumatic brain injury and persistent symptoms. Development [Internet]. 2011;1–156. Available from:https://doi.org/10.1016/j.apmr.2019.10.179
47. Chateauvieux S, Morceau F, Diederich M. Valproic Acid. Encycl Toxicol Fourth Ed Vol 1-9 [Internet]. 2024 Mar 19 [cited 2025 Aug 6];9:V9-705-V9-713. Available from: https://doi.org/10.1016/B978-0-12824315-2.00578-9
48. Safdar A, Ismail F. A comprehensive review on pharmacological applications and drug induced toxicity of valproic acid. Saudi Pharm J [Internet]. 2023 Feb 1 [cited 2025 Aug 5];31(2):265–78. Available from: https://doi.org/10.1016/j.jsps.2022.12.001
49. Badan Pengawas Obat dan Makanan. DEPAKENE (valproic acid) Label. 2023 Feb 02 [cited 2025 Nov 26]. Available from: https://registrasiobat.pom.go.id/files/assesment-reports/01731832504.pdf
50. Biesterveld BE, Pumiglia L, Iancu A, Shamshad AA, Remmer HA, Siddiqui AZ, et al. Valproic Acid Treatment Rescues Injured Tissues After Traumatic Brain Injury. J Trauma Acute Care Surg [Internet].
2020 Dec 1 [cited 2025 Aug 5];89(6):1156. Available from: https://doi.org/10.1097/TA.0000000000002918
